Search

Your search keyword '"Mark R. Silvis"' showing total 2 results
Start Over Author "Mark R. Silvis" Journal cancer cell
2 results on '"Mark R. Silvis"'

1. ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors

Author

Maria S. Tretiakova, Vassily Kutyavin, Ilsa Coleman, Jared M. Lucas, Liem T. Nguyen, Valeri Vasioukhin, Olga Klezovitch, Hamid Bolouri, Lawrence D. True, Peter S. Nelson, Colm Morrissey, and Mark R. Silvis

Subjects
Male, Transcriptional Activation, Cancer Research, Porphyrins, genetic structures, Cell Cycle Proteins, Mice, Transgenic, Biology, Translocation, Genetic, Article, Mice, Random Allocation, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Transcriptional Regulator ERG, medicine, Animals, Humans, Transcription factor, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Oncogene Proteins, Regulation of gene expression, YAP1, 0303 health sciences, Hippo signaling pathway, Age Factors, Prostatic Neoplasms, Verteporfin, Cancer, YAP-Signaling Proteins, Cell Biology, Phosphoproteins, medicine.disease, Xenograft Model Antitumor Assays, eye diseases, Up-Regulation, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Trans-Activators, Cancer research, sense organs, Erg, Signal Transduction, Transcription Factors
Abstract

SummaryThe significance of ERG in human prostate cancer is unclear because mouse prostate is resistant to ERG-mediated transformation. We determined that ERG activates the transcriptional program regulated by YAP1 of the Hippo signaling pathway and found that prostate-specific activation of either ERG or YAP1 in mice induces similar transcriptional changes and results in age-related prostate tumors. ERG binds to chromatin regions occupied by TEAD/YAP1 and transactivates Hippo target genes. In addition, in human luminal-type prostate cancer cells, ERG binds to the promoter of YAP1 and is necessary for YAP1 expression. These results provide direct genetic evidence of a causal role for ERG in prostate cancer and reveal a connection between ERG and the Hippo signaling pathway.

Published
2015

2. Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Author

Sheri L. Holmen, Steffi Treitschke, Clemens A. Schmitt, Ellen van Rooijen, Kolja Schleich, Sujuan Ji, Philipp Lohneis, Christian Speck, Soyoung Lee, Yardena Samuels, Melanie Werner-Klein, Kristel Kemper, Bin Yue, Nouar Qutob, Daniel S. Peeper, Frédérick A. Mallette, Lianjie Li, Leonard I. Zon, Abdel G. Elkahloun, Yong Yu, Svenja Meierjohann, Maurice Reimann, Dhriti Dhawan, Mark R. Silvis, Bernd Dörken, Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, and Publica

Subjects
0301 basic medicine, Cancer Research, Jumonji Domain-Containing Histone Demethylases, Skin Neoplasms, Cell, LSD1, Ras/Braf, Histones, 0302 clinical medicine, Histone demethylation, Promoter Regions, Genetic, Zebrafish, Melanoma, Cellular Senescence, Histone Demethylases, histone demethylation, targeted therapy, animal models, Cell biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Melanocytes, Senescence, patient-derived xenograft, Mice, Nude, Biology, Methylation, Article, Histone H3, 03 medical and health sciences, Downregulation and upregulation, medicine, Gene silencing, Animals, Humans, Oncology & Carcinogenesis, neoplasms, animal model, Lysine, JMJD2C, Cell Biology, Melanoma cancer, biology.organism_classification, medicine.disease, H3K9, 030104 developmental biology, biology.protein, Cancer research, Demethylase, 1109 Neurosciences, 1112 Oncology And Carcinogenesis
Abstract

Oncogene-induced senescence, e.g., in melanocytic nevi, terminates the expansion of pre-malignant cells via transcriptional silencing of proliferation-related genes due to decoration of their promoters with repressive tri-methylated histone H3 lysine 9 (H3K9) marks. We show here that structurally distinct H3K9-active demethylases—the lysine-specific demethylase-1 (LSD1) and several Jumonji C domain-containing moieties (such as JMJD2C)—disable senescence and permit Ras/Braf-evoked transformation. In mouse and zebrafish models, enforced LSD1 or JMJD2C expression promoted Braf-V600E-driven melanomagenesis. A large subset of established melanoma cell lines and primary human melanoma samples presented with a collective upregulation of related and unrelated H3K9 demethylase activities, whose targeted inhibition restored senescence, even in Braf inhibitor-resistant melanomas, evoked secondary immune effects and controlled tumor growth in vivo.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results